The specific objectives of our research are to define the mode of action and structure-activity relationships for certain antitumor and antiviral agents and to explore the molecular basis for their interaction with macromolecules. Among the agents to be studied are: (a) cytotoxic proteins (ricin, cessalin and Phytolacca americana peptide) (b) antitumor agents (maytansine and myxin) and (c) potential antivirals (bleomycin, aurintricarboxylic acid and heterocyclic dyes that act through photoinactivation). The interaction of some of these compounds with presumptive receptors (e.g. bleomycin with DNA and ricin with galactosides) will be studied by high resolution nuclear magnetic resonance spectroscopy and other biophysical techniques. Determining the mode of action of such compounds may be of value in establishing normal pathways of macromolecular synthesis as well as in correlating biochemical properties of drugs with therapeutic activity. Knowledge of the mode of action suggests new uses for some drugs and may warn against unsuspected toxicities. Information gained from these studies may provide clues that will lead to the development of new chemotherapeutic agents with antiviral activity. BIBLIOGRAPHIC REFERENCES: PMR Studies of Carbonic Anhydrase III. Binding of Sulfonamides. Pedsando, J.M., and Grollman, A.P. J. Biol. Chem. 14, 689-693 (1975). Interactions of Saccharides with Concanavalin A III. Relation Between Calcium Ions and the Binding of Saccharides to Concanavalin A. Brewer, C.F., Sternlicht, H., Marcus, D.M. and Grollman, A.P. J. Biol. Chem. 249, 4614-4616 (1974).